tbuckley/cabot-search huggingface dataset:
Abstract 11758: Sex Differences in the Associations Between Uric Acid and Incidence of Hypertension, Diabetes, and Chronic Kidney Disease in a Healthy Japanese Population
Authors: ANWAR A SALIM, Shin Kawasoe, Takuro Kubozono, Satoko Ojima, Takeko Kawabata, Yoshiyuki Ikeda, Hironori Miyahara, Koichi Tokushige, Mitsuru Ohishi
Journal: Circulation (2022)

Introduction: Uric acid (UA) has been linked to the development of cardiometabolic diseases. However, the effects of UA levels by sex have not been reported. Hypothesis: We hypothesized that UA plays a critical role in the development of hypertension, diabetes, and chronic kidney disease (CKD) in Japanese men and women who are apparently healthy at baseline. Methods: This retrospective cohort study included individuals who participated in a health checkup at the Kagoshima Kouseiren Hospital from October 2008 to April 2019 who had a 5-year follow-up. We excluded participants with hypertension, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m2, history of gout, hyperuricemia medication, and missing data at baseline. Uric acid levels were divided into quartiles as follows: men: 1st quartile UA &lt; 4.8 mg/dL, 2nd quartile 4.9-5.6 mg/dL, 3rd quartile 5.7-6.4 mg/dL, and 4th quartile UA &gt; 6.5 mg/dL; women: 1st quartile UA &lt; 3.4 mg/dL, 2nd quartile 3.5-4.0 mg/dL, 3rd quartile 4.1-4.7 mg/dL, and 4th quartile UA &gt; 4.8 mg/dL. To assess the association between baseline UA levels and the development of hypertension, diabetes, and CKD, we performed a multivariable logistic regression analysis adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure, current smoking, alcohol consumption, exercise habit, serum triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and eGFR by sex. Results: In total, 21,514 participants (age, 52.9±10.9 years; men, 39.8%), were enrolled. In men, the OR and 95% CI for the fourth to first quartile was associated with increased risk for hypertension (OR, 1.35; 95% CI, 1.13-1.62, P=0.0011), and CKD (OR, 1.42; 95% CI, 1.04-1.95, P=0.0287), and inversely related with diabetes (OR, 0.60; 95% CI, 0.39-0.93, P=0.0221). In women, the OR and 95% CI for the fourth to first quartile showed no association with neither hypertension (OR, 1.14; 95% CI, 0.95-1.36, P=0.1541), diabetes (OR, 0.97; 95% CI, 0.53-1.77, P=0.9271), nor CKD (OR, 1.26; 95% CI, 0.97-1.65, P=0.0828). Conclusion: Elevated serum UA indicates the risk of future hypertension and CKD, and an inverse relation with diabetes in apparently healthy Japanese men.
Abstract 11257: Septal Ischemia in Acute Coronary Syndromes and the Risk of Cardiac Arrest
Authors: Kavin Sundaram, Syed Rafay Ali Sabzwari, Ryan G Aleong, Alexis Tumolo, Michael Rosenberg, Matthew Zipse, Wendy Tzou, Lohit Garg
Journal: Circulation (2022)

Introduction: The interventricular septum may play an important role in circuits that lead to ventricular tachycardia and ventricular fibrillation. Hypothesis: Among patients with ST-segment myocardial infarction elevation (STEMI), those presenting with cardiac arrest are more likely to have septal ischemia, defined as ST-elevation &gt; 1 mm in V1, than those with other clinical presentations. Methods: A single-center retrospective review was conducted for all patients presenting with a STEMI from January 1, 2016-December 31, 2021. This identified a total of 60 consecutive patients with pre-intervention cardiac arrest and the first 60 patients in this time frame who presented without cardiac arrest. Both groups had had similar baseline characteristics. ( Table 1). Results: A higher proportion of patients presenting with cardiac arrest had evidence of septal ischemia ( Figure 1, 29/60 versus 17/60, p&lt;0.02). These findings remained statistically significant in a sub-group analysis of patients drawn from the same series with lesions of the right coronary artery (RCA) and left circumflex (LCx) without proximal left anterior descending (LAD) lesions ( 7/23 versus 2/32, p&lt;0.02 ) . Conclusions: Patients presenting with cardiac arrest in the setting of ACS were more likely to have evidence of septal ischemia.
Abstract 11324: Association of Patient Reported Outcomes With NYHA Class and Functional Capacity in Symptomatic Obstructive Hypertrophic Cardiomyopathy: An Analysis of Spirit-HCM Study
Authors: Albree Tower Rader, Natalie Szpakowski, Zoran B Popovic, Barbara Bittel, Agostina Fava, Bo Xu, Maran Thamilarasan, Amgad Mentias, Nicholas G Smedira, Milind Y Desai
Journal: Circulation (2022)

Introduction: Patient reported outcomes (PRO) are used to assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM). Hypothesis: In symptomatic oHCM patients, we sought to prospectively study the association between various PROs &amp; their association with physician reported New York Heart Association (NYHA) class. Methods: This was a prospective study (ClinicalTrials.gov: NCT03092843) of symptomatic oHCM patients undergoing myectomy (n=173, mean 51 years, 62% men) between 3/2017 &amp; 6/2020. At baseline, we recorded: a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] score c) Duke Activity Status Index [DASI] &amp; d) European QOL score [EQ-5D], in addition to NYHA class, 6-minute walk test (6MWT) distance &amp; peak left ventricular outflow tract gradient (PLVOTG). Results: The median baseline KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D scores were 50, 37, 44, 25 &amp; 0.61, respectively; 6MWT distance was 366 m. Figure 1 demonstrates highly significant correlations between various PROs, only modest correlations of PROs with 6MWT &amp; PLVOTG. Figure 2 shows that ~1/3rd patients with NYHA class II had worse than median PROs, while ~1/3 rd in NYHA III/IV had PROs better than median. Conclusions: In symptomatic oHCM patients, there is a high internal correlation between various prospectively recorded PROs but a modest correlation with 6MWT &amp; LVOTG. Also, in symptomatic oHCM, NYHA class incompletely characterizes disease severity, and using a more sensitive metric like PROs may help to better identify patients with impaired QOL who will potentially benefit from myectomy.
Abstract 12655: Lipomatous Metaplasia in Chronic Infarcts is Associated With Prolonged Activation Recovery Interval Within Ventricular Tachycardia Corridors
Authors: Lingyu Xu, Sohail Zahid, MirMilad Pourmousavi Khoshknab, Juwann Moss, Ronald D Berger, Jonathan Chrispin, David J Callans, Francis E Marchlinski, Stefan Zimmerman, Yuchi Han, Benoit Desjardins, Natalia Trayanova, Saman Nazarian
Journal: Circulation (2022)

Introduction: We studied the association of infarct scar versus lipomatous metaplasia (LM) with the activation recovery interval (ARI) in putative ventricular tachycardia (VT) corridors traversing the infarct zone. Methods: The cohort included 32 patients from the prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Ischemic Cardiomyopathy (INFINITY) study. We defined myocardial scar, border zone (BZ) and potential viable corridors through infarct by late gadolinium enhancement (LGE)-cardiac magnetic resonance (CMR), and LM by computed tomography (CT). The images were registered with electroanatomic maps wherein the ARI of each point (1,530 within LM, 4,946 within scar) was calculated using a custom Python code as the time interval from the minimum derivative within the QRS to the maximum derivative within the T wave. ARI dispersion was defined as the standard deviation (SD) of ARI per AHA segment. Multilevel random effects linear regression models, clustered by patient, were used to evaluate the association between ARI (or ARI dispersion) with tissue types. Results: LM exhibited higher myocardial ARI than normal myocardium, BZ, scar [regression coefficient: 35.5 vs. 0, 11.4, and 25.4, P &lt;0.001]. Of 100 corridors computed from LGE-CMR and electrophysiologically confirmed to participate in VT reentry, 97 traversed through or near LM, and displayed prolonged ARI compared to 123 non-critical corridors distant from LM [356 (319, 396) vs. 283 (266, 316) ms, P &lt;0.001, Figure 1]. The association of LM with Log(ARI SD ) was more robust than that of scar (likelihood ratio χ 2 47.5 vs. 23.4, and 5.9% vs. 1.6% increase in Log(ARI SD ) /1 cm 2 increase per AHA segment, respectively). Additionally, LM and scar exhibited interaction (p&lt;0.001) in their association with Log(ARI SD ). Conclusion: LM is closely associated with prolonged local action potential duration of corridors and ARI dispersion, which may facilitate the propensity of VT circuit reentry.
Abstract 12626: A Systematic Review and Meta-analysis of Factors Associated With Long-Term Mortality in Adults After Coronary Artery Bypass Graft Surgery
Authors: Suprateeka Talukder, Arnaldo Dimagli, Umberto Benedetto, Alastair Gray, Stephen Gerry, Belinda Lees, Lukasz Krzych, Mario F Gaudino, David Taggart, Marcus D Flather
Journal: Circulation (2022)

Background: With an ageing and increasingly multi-morbid population, the use of coronary artery bypass grafting (CABG) is expected to increase. As short-term CABG mortality rates have decreased, estimating long-term outcomes for patients with specific risk factors has become more relevant. Previous single observational studies have identified risk factors for adverse long-term outcomes, such as older age and diabetes. Purpose: Understanding the pre-operative characteristics that affect late mortality post-CABG can lead to effective risk stratification and enhancement of secondary prevention programmes, thereby aiming to improve long-term prognosis after the procedure. Methods: MEDLINE, Embase, Google Scholar, and Cochrane electronic databases were searched to identify all relevant articles evaluating associations between pre-operative risk factors and long-term mortality (≥5 years ) post-CABG. Studies with &lt;500 patients were excluded. Results: From 1193 potentially eligible articles, 43 studies met the inclusion criteria. A total of 360,481 patients, with an average follow-up of 10 years, were included, representing an approximate cumulative total of 3,604,810 person-years. After pooling adjusted hazard ratios, 6 major risk factors were found to be independently associated with long-term mortality after CABG: age, ischaemia (peripheral vascular disease, prior cerebrovascular accident, left main stem coronary disease), diabetes mellitus, atrial fibrillation, renal impairment (chronic kidney disease and dialysis-dependent chronic kidney disease), and impaired left ventricular function (reduced LV ejection fraction or prior heart failure) (see Table 1). Conclusion: We have identified six groups of risk factors for long-term mortality post-CABG. Further work is needed to assess whether the influence of these risk factors varies over time and if targeted interventions for high-risk groups lead to improved long-term mortality.
Abstract 11538: The Impacts of the Patient Voice in Continuing Medical Education (CME) to Enhance Homozygous Hypercholesterolemia (HoFH) Diagnosis and Management
Authors: Carole Drexel, Emily Bixler, Martha Gulati, Deepak L Bhatt, Peter P Toth
Journal: Circulation (2022)

Introduction: Early diagnosis and management of HoFH are key to achieving CV risk reduction. However, barriers to identifying probable cases, low awareness of current guidelines, and a lack of knowledge of treatment options continue to present challenges to HCPs. Hypothesis: CME with the patient voice can enhance HCP's competence in diagnosing and managing HoFH and adopting newest treatment options. Methods: A 60-minute CME activity that incorporated the patient voice was launched live-online 7/20/21 and was available on-demand for 1 year. Test questions were administered before and immediately after the activity. A follow-up survey on HCP behavior was sent to post-test respondents 2 months after activity completion. Responses were analyzed for engagement, lessons learned, and continuing gaps. Chi-square tests compared paired responses (P less than 0.05; pre/post). Results: As of 6/6/22, 1,806 HCPs had engaged (14% cardiologists and 57% PCPs managing an average of 50.2 patients per year with very high lipid levels). At entry, 68% of HCPs were at least “somewhat confident” in managing HoFH, while 48% did not know about newly approved agents for HoFH. Outcomes showed significant increases (pre vs post) in ability to recognize manifestations of HoFH (47% vs 87%), apply guidelines to reduce high LDL-C levels despite statin therapy (38% vs 92%), and recognize mechanism of action of evinacumab (43% vs 88%). On follow up, HCPs reported positive impacts on practice related to diagnosing HoFH, applying guideline-driven care to lower LDL-C, identifying high-risk patients, and referring appropriately. Conclusions: Live and on-demand CME including the voice of the patient successfully highlighted HoFH patient’s expectations of care and enhanced HCPs’ ability to adapt to the changing HoFH landscape. Additional education on this evolving landscape and associated guidelines can further enhance quality of care for HoFH patients.
Abstract 12012: Subphenotypes of Heart Failure With Reduced Ejection Fraction Based on Repeated Measurements of 4210 Circulating Proteins Are Driven by Protein Subsets Reflecting Different Biological Mechanisms
Authors: Teun B Petersen, Marie de Bakker, Folkert W Asselbergs, K. Martijn Akkerhuis, Jasper J Brugts, Jan van Ramshorst, Tom Lumbers, Rachel Ostroff, Peter D Katsikis, Peter J van der Spek, Victor A Umans, Eric Boersma, Dimitris Rizopoulos, Isabella Kardys
Journal: Circulation (2022)

Introduction: Subphenotyping of HF may lead to pathophysiological insights and treatment opportunities. We aimed to identify novel circulating-protein based subphenotypes (SP) in patients with HFrEF. We used repeated proteomic assessments to account for the dynamic nature of HF. Methods: In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring and applied an aptamer-based multiplex proteomic approach. We used unsupervised machine learning to derive subphenotypes from 4210 protein trajectories per patient represented by linear mixed effect intercept and slope coefficients. Results: We identified 4 SPs. SP1 was older with higher SBP, EF and history of hypertension. SP2 was older with lower SBP, lower EF, more comorbidities, and worse prognosis (adjHR(95% CI): 4.06 (2.07-7.96)) compared to SP1. SP3 was younger, had lower SBP and EF, more frequently cardiomyopathy (in particular dilated), and a worse prognosis (2.70 (1.33-5.48)). SP4 contained few patients and thus was harder to interpret. It differed from SP3 via higher SBP, higher EF, and seemingly better prognosis. SP allocation was driven by subsets of proteins associated with various biological functions and diseases, e.g. myocardial stress, inflammation, and renal dysfunction. Clinical characteristics of the SPs were aligned with these associations. The prognostic model using SPs based on repeated measurements had a better fit than using SPs based on baseline values (c-index: 0.78 vs 0.72). Conclusions: We found 4 circulating-protein based HFrEF subphenotypes driven by varying protein subsets, with different clinical characteristics and prognosis. Repeated protein measurements improved discriminative ability of the subphenotypes for clinical outcomes.
Abstract 12079: The Sexual Dimorphism of IgG1 Anti-angiogenic Activity Depends on Y Chromosome Genes
Authors: Dionne A Argyle, Felipe Pereira, Shao-bin Wang, Jayakrishna Ambati, Bradley D Gelfand
Journal: Circulation (2022)

Section: Angiogenesis, Vascular Development and Regeneration Introduction: IgG1 antibodies possess sexually dimorphic anti-angiogenic activity independent of antigen binding. Mosaic loss of Y chromosome (LOY) is associated with numerous cardiovascular-related diseases, and the male specific region of the Y chromosome (MSY) contributes to hypertension, atherosclerosis, cancer, and male infertility. The biological mechanisms underlying these associations is largely unknown and not fully understood. A better understanding of the role of protein coding genes in the Y chromosome and angiogenesis regulation may lead to a better understanding of these associations and better treatments. Hypothesis: The loss of function of genes in the MSY of males impairs the anti-angiogenic activity IgG1 antibodies. Methods: MSY transcripts were quantified in human macrophages and primary bone marrow derived macrophages (BMDMs) from C57BL/6J male mice by qPCR. MSY genes were inhibited by siRNAs targeting DDX3Y, KDM5D, and UTY, followed by treatment with a human IgG1 in a chemotaxis assay. Laser photocoagulation-induced choroidal neovascularization (CNV) was performed in male C57BL/6J followed by intravitreous injection of full-length humanized IgG1 antibody along with a cell-permeable siRNA scrambled control or siRNA targeting DDX3Y. Results: Male macrophages from human and mouse transcribe multiple Y chromosome genes. Silencing of multiple MSY-encoded genes abrogated the ability of IgG1 to suppress chemotaxis and angiogenesis, rendering male systems to respond similarly to female systems. Male macrophages from DDX3Y knockout mice were also resistant to IgG1 treatment. siRNA targeting DDX3Y suppressed inhibition in male mice. Conclusions: The antiangiogenic activity IgG1 antibodies is greatly reduced by antagonizing Y chromosome genes. These studies highlight protein coding genes of the Y chromosome as a potential angiogenesis modulating target responsible for sexually dimorphic responses.
Abstract 12260: The SMARTER Trial: Is Engagement With Mhealth Better With Daily Feedback to Self-Monitoring Compared to No Feedback?
Authors: Lora E Burke, Molly B Conroy, Zhadyra Bizhanova, Jacob K Kariuki, Jessica Cheng, Britney Beatrice, Susan M Sereika
Journal: Circulation (2022)

Introduction: Self-monitoring (SM) is the cornerstone of behavior change for weight loss as is providing feedback (FB) to SM. FB to SM can be delivered remotely and in real time. Hypothesis: Participants assigned to SM+FB will show greater engagement in the weight loss intervention, as measured by adherence to dietary goals, than the SM group. Methods: SMARTER was a 2-arm trial that randomized 502 adults aged ≥18 years with a body mass index (BMI) 27-43 kg/m 2 to 1) self-monitoring of diet and physical activity with up to 3 daily FB messages (SM+FB: n=251) or 2) self-monitoring only (SM: n=251). Daily calorie goals were based on baseline body weight and gender; the fat goal was 25% of caloric intake. Monthly adherence to calorie and fat goals were defined as number of days with intake within 85% -115% of daily goals divided by number of valid days (≥15 days with ≥50% of daily goals recorded) multiplied by 100%. Linear mixed modeling with random intercept and slope was used to examine the effect of treatment assignment on adherence over 12 months. Results: Participants were predominantly female (79%) and White (83%) with a mean age of 45±14.4 years and a mean BMI of 33.7±3.96 kg/m 2 . Monthly percentages of days adherent to calorie goal (b [95% CI]: -2.07 [-3.58, -0.56], b^2: 0.34 [0.08, 0.59], b^3: -0.02 [-0.03, -0.01], all P&lt;.05 ) and fat goal (b: 2.14 [1.03, 3.25], b^2: -0.31 [-0.50, -0.12], b^3: 0.01 [0.003, 0.02], all P&lt;.05 ) decreased curvilinearly over time. On average, SM+FB had greater monthly percentages of days adherent to calorie goal (4.42 [0.41, 8.45], P=.03 ) and fat goal (3.90 [1.44, 6.36], P&lt;.05 ) than SM. Moreover, the rate of decline in monthly percentages of days adherent to calorie (b: -1.98 [-3.03, -0.93], b^2: -0.14 [0.06, 0.22], all P&lt;.05 ) and fat (b: -1.18 [1.94, -0.42], b^2: 0.10 [0.04, 0.16], all P&lt;.05 ) goals were non-linear but different between groups. Conclusions: Personalized FB messages were effective in promoting adherence to dietary goals; however, overall engagement with the intervention was low, which may explain small between group differences.
Abstract 12070: Post-Cardiac Arrest Sedation Modulates Electroencephalographic Slow-Wave Activity and Promotes Neurological Recovery in a Mouse Model of Cardiac Arrest
Authors: Takamitsu Ikeda, Edilberto Amorim, Yusuke Miyazaki, Risako Kato, Eizo Marutani, Michael G Silverman, Rajeev Malhotra, Ken Solt, Fumito Ichinose
Journal: Circulation (2022)

Introduction: The majority of patients resuscitated from cardiac arrest (CA) present in coma or with an altered level of consciousness. Although CA survivors are routinely sedated during targeted temperature management, the effects of sedation on CA outcomes remain to be determined. Hypothesis: Post-CA sedation would modulate cerebral physiology and improve neurological outcomes in mice. Methods: Adult C57BL/6J mice of both sexes were subjected to potassium chloride-induced CA and thereafter resuscitated with manual chest compression. Starting at return of spontaneous circulation (ROSC) or at 60 minutes after ROSC, mice received intravenous infusion of propofol at 40 mg · kg -1 · h -1 , dexmedetomidine at 1 μg · kg -1 · h -1 , or normal saline for 2 hours. Body temperature was lowered and maintained at 33°C during sedation. Cerebral blood flow was measured for 4 hours after ROSC. Telemetric electroencephalogram (EEG) was recorded in freely moving mice from 3 days before up to 7 days after CA. Results: Sedation with propofol or dexmedetomidine starting at ROSC attenuated brain injury and improved survival in hypothermia-treated post-CA mice (propofol [13/16] vs. no sedation [4/16], P = 0.008; dexmedetomidine [14/16] vs. no sedation [4/16], P = 0.002). Mice that were not sedated after ROSC exhibited cerebral hyperemia immediately after resuscitation and EEG power in all frequency bands remained less than 20% of the baseline in the first 4 hours after ROSC. Administration of propofol or dexmedetomidine starting at ROSC attenuated cerebral hyperemia and induced slow-wave (0.5-4 Hz) EEG activity that reached near baseline levels during and early after sedation. Increased EEG activity within 6 hours after ROSC was associated with improvement in neurological outcomes at 24 hours post-CA. In contrast, delayed sedation starting at 60 minutes after ROSC failed to improve outcomes, without attenuating cerebral hyperemia and inducing slow-wave EEG activity. Conclusions: Post-CA sedation with propofol or dexmedetomidine improved neurological outcomes and survival in mice resuscitated from CA and treated with hypothermia. The beneficial effects of sedation were accompanied by attenuation of the cerebral hyperemic response and induction of EEG slow-wave activity.